Autoimmune disorders of the CNS have complex pathogeneses that are not well understood. In multiple sclerosis and neuromyelitis optica spectrum disorders, T cells destroy CNS tissue, resulting in severe disabilities. Mounting evidence suggests that reducing inflammation in the CNS may start with modulation of the gut microbiome. The lymphoid tissues of the gut are specialized for the induction of regulatory cells, which are directly responsible for the suppression of CNS-damaging autoreactive T cells. Whether cause or effect, the onset of dysbiosis in the gut of patients with multiple sclerosis and neuromyelitis optica provides evidence of communication along the gut-brain axis. Thus, current and future therapeutic interventions directed at microbiome modulation are of considerable appeal.